DESCRIPTION: (Applicant's Description) The principal objective of this research plan is to design a targeted drug delivery system for specific recognition of leukemia cells. The targeting molecule to be prepared consists of a single chain antibody fused to a hydrophobic domain which can then be formulated into a liposome. The objectives of the Phase I proposal are to: construct the targeting molecule; formulate it into a liposome; and verify the ability of this construct to selectively bind leukemia cells expressing the CD33 receptor. If successful, this novel targeting technology should allow: (1) the commercial production of large quantities of purified targeting molecules using standard protein isolation techniques; (2) maximum flexibility for the insertion of different targeting motifs within a standard gene cassette for the rapid development of new drug delivery vehicles; (3) easy incorporation of the targeting molecules into liposomes used for drug delivery, resulting in a commercially viable process for large scale production and; (4) elimination of the cumbersome chemical modification procedures that need to be made with other systems. Achievement of these objectives could result in a liposome-based targeting system with widespread applications for the treatment of numerous diseases, including cancer. PROPOSED COMMERCIAL APPLICATION: The protential commercial advantages of the technology to be developed include: an increased margin of safety because the targeted liposomes should have minimal toxic side effects; relatively straightforward procedures which make the production process less costly; and enhanced efficacy because of the improvement in targeted delivery. The proposed technology is also flexible; new targeting molecules can be made quickly and easily by simply "cutting and pasting" new binding sequences at the proper sites in the expression vector. Given the ability to rapidly design and engineer new targeting molecules, the potential applications for this technology range from treatment of pathogenic diseases to cancers.